Quick and convenient construction of lambda-cyhalothrin antigen for the generation of specific antibody.

Lambda-cyhalothrin is a pyrethroid widely used in crop, fruit and vegetable production, but has potential health threats to human. Immunoassay is a cheap, rapid and facile method to detect lambda-cyhalothrin, yet wide application of this method still requires improvement in the construction of antigen. In this study, we developed a one-step lambda-cyhalothrin hapten synthesis that transformed the cyanide group in lambda-cyhalothrin to amide. Complete antigen was assembled by coupling the amide with succinic-anhydride-activated carrier proteins, and corresponding polyclonal antibodies were generated using Balb/c mice. Using antibody generated by the method in this paper, the competitive ELISA demonstrated the lowest detection limit of 3.772 µg/L for lambda-cyhalothrin, and no significant cross-reactivity for other pyrethroid pesticides was observed. All the results suggested we have established a more efficient technique of generating lambda-cyhalothrin antibody. Furthermore, since the activated proteins used in this study are highly controllable, we believe these proteins could potentially be the prototype of a series of standardized carrier proteins for the synthesis of complete antigens.

Synthesis and Stereostructure-Activity Relationship of Novel Pyrethroids Possessing two Asymmetric Centers on a Cyclopropane Ring.

2-Methylcyclopropane pyrethroid insecticides bearing chiral cyanohydrin esters or chiral ethers and two asymmetric centers on the cyclopropane ring, were synthesized. These compounds were designed using a "reverse connection approach" between the isopropyl group in Fenvalerate, and between two dimethyl groups in an Etofenprox analogue (the methyl, ethyl form), respectively. These syntheses were achieved by accessible ring opening reactions of commercially available (±)-, (R)-, and (S)-propylene oxides using 4-chlorobenzyl cyanide anion as the crucial step, giving good overall yield of the product with >98% ee. The insecticidal activity against the common mosquito (Culex pipiens pallens) was assessed for pairs of achiral diastereomeric (1R*,2S*)-, (1R*,2R*)-cyanohydrin esters, and (1R*,2S*)-, (1R*,2R*)-ethers; only the (1R*,2R*)-ether was significantly effective. For the enantiomeric (1S,2S)-ether and (1R,2R)-ether, the activity was clearly centered on the (1R,2R)-ether. The present stereostructure‒activity relationship revealed that (i) cyanohydrin esters derived from fenvalerate were unexpectedly inactive, whereas ethers derived from etofenprox were active, and (ii) apparent chiral discrimination between the (1S,2S)-ether and the (1R,2R)-ether was observed. During the present synthetic study, we performed alternative convergent syntheses of Etofenprox and novel 4-EtO-type (1S,2S)- and (1R,2R)-pyrethroids from the corresponding parent 4-Cl-type pyrethroids, by utilizing a recently-developed hydroxylation cross-coupling reaction.

Molecular mechanism of synthetic pyrethroid and organophosphate resistance in field isolates of Rhipicephalus microplus tick collected from a northern state of India.

The frequently used chemical control method to manage Rhipicephalus microplus is limited by the emergence of resistance populations. Understanding of resistance mechanisms is essential to develop strategy for sustainable management. The present study was focused on working out the molecular mechanisms of resistance against synthetic pyrethroids (SPs) and organophosphates (OPs) in field isolates of R. microplus collected from six districts of Uttar Pradesh, India. Adult immersion test with discriminating concentrations (AIT-DC) was used to determine resistance status of isolates to SPs (deltamethrin, cypermethrin) and OPs (diazinon, coumaphos). All the six isolates were found resistant to SPs with resistance factor (RF) of 2.9-58.6 and to one of the OP compounds, diazinon having RF of 3.5-13.7 but susceptible to coumaphos (RF < 1.4). Three R. microplus genes, viz. para-sodium channel domain II S4-5 linker, carboxylesterase (372 bp) and acetylcholinesterase 2 (1692 bp) were sequenced and compared with respective sequences of reference susceptible IVRI-I, reference OP resistant population (IVRI-III), IVRI-IV and multi-acaricide resistant population (IVRI-V) of R. microplus. A C190A mutation in the domain II S4-5 linker region of sodium channel gene leading to L64I amino acid substitution was detected in all six isolates. The G1120A mutation in the carboxylesterase gene could not be detected in any isolate. Five nucleotide substitutions viz., G138A, G889A, T1090A, C1234T and G1403A were identified in the acetylcholinesterase 2 gene leading to four amino acid substitutions. The findings of the study corroborate the role of mutation in sodium channel and acetylcholinesterase 2 genes in SP and OP resistance in this part of India.

Biorational substitution of piperonyl butoxide in organic production: effectiveness of vegetable oils as synergists for pyrethrums.

Piperonyl butoxide is a semi-synthetic synergist for natural pyrethrum and synthetic pyrethroid insecticides in phytochemicals and biocides. As such it is used in large quantities for crop treatments, stored grain protection, disinfestation of grain storage facilities and indoor uses. Piperonyl butoxide is consequently a regular contaminant in stored grains, and subsequently in corresponding cereal food products and meat via feed uses. Therefore it is regularly monitored and its MRL is ongoing a reassessment. It is also considered as a possible human carcinogen and a suspected endocrine disruptor. For all these reasons and considerations most of the countries have already banned its use in Organic Farming as France in 2017. Thus, ecological substitution of with biorational and sustainable solutions is required. Vegetable oils have been described as exhibiting similar potency and synergistic effects. We have reviewed the literature and have proceeded to ecotoxicological efficacy tests in order to determine the best and most durable substitution candidates. Sesame and rape seed oil were determined to be the most efficient.

Efficacy of commercial synthetic pyrethroids and organophosphates associations used to control Rhipicephalus (Boophilus) microplus in Southern Brazil / Eficácia de associações comerciais entre piretroides sintéticos e organofosforados utilizados no controle de Rhipicephalus (Boophilus) microplus na Região Sul do Brasil

Abstract This study evaluated the acaricidal efficiency of synthetic pyrethroids (SP) associated with organophosphates (OP) against Rhipicephalus (Boophilus) microplus populations in the state of Rio Grande do Sul, Southern Brazil. Ticks were collected in 54 cattle farms and tested using in vitro adult immersion test against four commercially available acaricide mixtures of SP and OP. Only one of four acaricides, comprising a mixture of cypermethrin, chlorpyrifos, and fenthion, had a mean efficiency higher than 95%, and was effective in 94.44% (51/54) of the cattle farms tested. The acaricide with a mixture of cypermethrin, chlorpyrifos, and citronelall had the lowest mean efficiency (62.11%), and was effective in 29.62% (16/54) of cattle farms tested. Furthermore, R. (B.) microplus in Southern Brazil exhibited differing degrees of resistance to SP and OP mixtures. The results suggest that the presence of fenthion contributes to the higher efficiency of the formulation with this active principle. This is possibly due to its recent commercial availability, as tick populations have been lower challenged with this product. Monitoring the resistance of ticks to carrapaticides is essential to maximize the efficiency of these products in the control of R. (B.) microplus.

Resumo Este estudo avaliou a eficiência acaricida de piretroides sintéticos (SP) associados a organofosforados (OP) sobre populações de Rhipicephalus (Boophilus) microplus no estado do Rio Grande do Sul, Brasil. Carrapatos foram coletados em 54 fazendas de bovinos, testados in vitro pelo teste de imersão de teleóginas, contra quatro associações acaricidas comercialmente disponíveis de SP e OP. Apenas um dos quatro acaricidas, constituído por associação de cipermetrina, clorpirifós e fenthion, teve eficiência média superior a 95%, sendo eficaz em 94,44% (51/54) das fazendas testadas. O acaricida com associação de cipermetrina, clorpirifós e citronelal teve menor eficiência média (62,11%), sendo efetivo em 29,62% (16/54) das fazendas testadas. Além disso, o R. (B.) microplus no sul do Brasil, apresentou diferentes graus de resistência às associações de SP e OP. Os resultados sugerem que a presença do fenthion contribui para a maior eficiência da formulação com esse princípio ativo. Possivelmente, isso ocorre em função da sua recente introdução no mercado, já que as populações de carrapatos foram pouco desafiadas com este produto. Monitorar a resistência dos carrapatos aos carrapaticidas é fundamental para maximizar a eficiência desses produtos no controle de R. (B.) microplus.

Efficacy of commercial synthetic pyrethroids and organophosphates associations used to control Rhipicephalus (Boophilus) microplus in Southern Brazil.

This study evaluated the acaricidal efficiency of synthetic pyrethroids (SP) associated with organophosphates (OP) against Rhipicephalus (Boophilus) microplus populations in the state of Rio Grande do Sul, Southern Brazil. Ticks were collected in 54 cattle farms and tested using in vitro adult immersion test against four commercially available acaricide mixtures of SP and OP. Only one of four acaricides, comprising a mixture of cypermethrin, chlorpyrifos, and fenthion, had a mean efficiency higher than 95%, and was effective in 94.44% (51/54) of the cattle farms tested. The acaricide with a mixture of cypermethrin, chlorpyrifos, and citronelall had the lowest mean efficiency (62.11%), and was effective in 29.62% (16/54) of cattle farms tested. Furthermore, R. (B.) microplus in Southern Brazil exhibited differing degrees of resistance to SP and OP mixtures. The results suggest that the presence of fenthion contributes to the higher efficiency of the formulation with this active principle. This is possibly due to its recent commercial availability, as tick populations have been lower challenged with this product. Monitoring the resistance of ticks to carrapaticides is essential to maximize the efficiency of these products in the control of R. (B.) microplus.

New Pyrethroids for Use Against Tuta Absoluta (Lepidoptera: Gelechiidae): Their Toxicity and Control Speed.

Insect pests are responsible for major losses in crop productivity, and insecticides are the main tools used to control these organisms. There is increasing demand for new products for pest management. Therefore, the aim of this study was to assess the toxicity of pyrethroids with acid moiety modifications to measure the insecticidal activity of these compounds on Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae). First, we synthesized E/Z mixtures of five pyrethroids: [9], [10], [11], [12], and [13]. Then, we separated the cis and trans pyrethroid isomers of [9], [10], [11], and [12]. We assessed the toxicity of these compounds against T. absoluta. The E/Z mixtures of the five pyrethroids (30 µg of substance per mg-1 of insect) caused high (100%) and rapid (<12 h) tomato borer mortality. The cis isomer of pyrethroid [10] was the most toxic to T. absoluta, causing mortality similar to permethrin. The other isomers were less powerful than permethrin.

[EFFECT OF PYRETHROIDS ON TAIGA TICKS (IXODES PERSULCATUS IXODIDAE)].

Nonspecific prevention of infections, the agents of which are transmitted by Ixodes ticks, is aimed at stopping the suction of the ticks to humans and is substantially based one the use of acaricides. The most interesting group of compounds to be used to individually protect humans is pyrethroids that cause different nerve conduction disturbances in the ticks, which result in their paralysis and death more significantly rapidly than the compounds from other chemical groups. The effect of 8 pyrethroids was investigated when the taiga ticks were in contact with the tissue treated with the compounds. The relationship of the chemical structure of pyrethroids with their acaricidal activity was analyzed from motor activity values and knockdown time. The test pyreithroids, in order of decreasing acaricidal activity, are imiprothrin cyphenothrin, cyfluthrin, alpha-cyperamethrin, zeta-cyperimethrin fenothrin, flumethrin.

Mg-Prompted Polyfluoroarene C-H Functionalization: Formal Synthesis of Transfluthrin, Fenfluthrin, and Tefluthrin.

Directing group and transition metal free C-H bond functionalization of a simple molecule is an ideal but challenging chemical transformation. Herein, we report a general Mg-prompted approach to synthesize versatile polyfluoroaryl carbinols at ambient temperature via polyfluoroarene C-H bond addition to aldehydes, which featured excellent monoaddition selectivity and broad functional group compatibility. The usefulness of this practical and efficient method was demonstrated in gram-scale formal synthesis of pyrethroid insecticides transfluthrin, tefluthrin, and fenfluthrin.

The effect of synthetic pyrethroids on the attachment and host-feeding behaviour in Dermacentor reticulatus females (Ixodida: Amblyommidae).

BACKGROUND: The high competence of D. reticulatus in transmission of tick-borne pathogens prompts investigations of the effect of chemicals used as repellents and acaricides on the behaviour of the tick on the host. Therefore, this paper presents the effect of permethrin and deltamethrin on the attachment and feeding in this tick species. FINDINGS: Attachment to rabbit skin of D. reticulatus females sprayed with pyrethroids and the effect of different doses thereof on feeding were assessed at a temperature of 20 ± 3 °C and 50% humidity. The dynamics of attachment of D. reticulatus females varied in a dose-dependent manner after the application of both pyrethroids. Within the first 0.5 h of the experiments, there was an over six-fold and over twelve-fold increase in the number of females attached to host skin after application of permethrin concentrations of 0.3906-0.7812 µg and 1.5625-3.1250 µg/1 specimen, respectively. In the case of deltamethrin, females treated with the dose of 0.0390 µg of the compound were able to attach to host skin only 4 hours after the infestation. The toxic activity of both pyrethroids increased the duration of the feeding period and decreased the body weight of engorged females and the feeding efficiency index. CONCLUSIONS: The accelerated attachment of D. reticulatus females caused by sublethal permethrin doses and delayed or inhibited attachment caused by deltamethrin suggest a necessity of careful selection of the type and dose of pyrethroids to protect hosts from tick attacks.

Polyenylcyclopropane carboxylic esters with high insecticidal activity.

BACKGROUND: Pyrethroids are synthetic derivatives of naturally occurring pyrethrum. These molecules are widely used in agriculture for ant, fly and mosquito control and for lawn and garden care. Pyrethroids are the optically active esters of 2,2-dimethyl-3-(2-methylpropenyl)-cyclopropane carboxylic acid, also known as chrysanthemic acid. However, their intense use has resulted in the development of resistance in many insect species. Herein, specific structural modifications of the pyrethroid scaffold and their effect on insecticidal activity, especially on resistant pests strains, are reported. RESULTS: The exposure to (1R)-trans-(E/Z)-2,3,5,6-tetrafluorobenzyl-3-(buta-1,3-dienyl)-2,2-dimethyl cyclopropanecarboxylate and its diastereomers produced 100% mortality in yellow fever mosquitoes (Aedes aegypti), house mosquitoes (Culex quinquefasciatus) and houseflies (Musca domestica). Moreover, this compound provided complete knockdown within 15 min of exposure against cockroaches (Blattella germanica) and maintained an excellent knockdown activity at 10 days after treatment. CONCLUSION: Novel pyrethroid derivatives obtained from 2,2-dimethyl-3-(2-methylpropenyl)-cyclopropanecarboxylic acid are described. These derivatives display high insecticidal activity, a wide spectrum of action and no toxicity towards mammalians. The proposed synthetic procedures are highly efficient and inexpensive, and therefore suitable for industrial scale-up.

Design, synthesis, and biological evaluation of various α-substituted benzylpyrroles based on the structures of insecticidal chlorfenapyr and natural pyrrolomycins.

On the basis of the structures of chlorfenapyr and dioxapyrrolomycin, a series of 2-benzylpyrroles with a hydroxyl, an alkyloxy, an acyloxy, an alkylsulfanyl, or an oxime moiety at the α-position of benzyl were designed and synthesized. Their insecticidal, acaricidal, and fungicidal activities were extensively investigated. The structure-activity relationship showed that benzylpyrroles bearing shorter α-alkyloxy groups gave better activities against most of the insect species; the alkylation of pyrrole usually gave increased activity. Among all compounds, (4-bromo-2-(α-(2,2,2-trifluoroethoxy)-4-chlorobenzyl)-1-(ethoxymethyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile) (5'j) exhibited the most outstanding insecticidal activities against oriental armyworm (IC50=10 mg L⁻¹), diamondback moth (0.07 mg L⁻¹), corn borer (50 mg L⁻¹), and mosquito (0.04 mg L⁻¹), which are very close to those of chlorfenapyr (5, 0.08, <25, and <0.025 mg L⁻¹, respectively). In addition, some compounds also exhibited a broad or selective fungicidal spectrum.

Synthesis of the insecticide prothrin and its analogues from biomass-derived 5-(chloromethyl)furfural.

Prothrin, a synthetic pyrethroid insecticide, was synthesized from the biomass-derived platform chemical 5-(chloromethyl)furfural in six steps and overall 65% yield. Two structural analogues of prothrin were also prepared following the same synthetic approach. Preliminary testing of these furan-based pyrethroids against the yellow fever mosquito Aedes aegypti indicates promising insecticidal activities.

Synthesis and insecticidal activity of an oxabicyclolactone and novel pyrethroids.

Deltamethrin, a member of the pyrethroids, one of the safest classes of pesticides, is among some of the most popular and widely used insecticides in the World. Our objective was to synthesize an oxabicyclolactone 6 and five novel pyrethroids 8–12 from readily available furfural and D-mannitol, respectively, and evaluate their biological activity against four insect species of economic importance namely A. obtectus, S. zeamais, A. monuste orseis, and P. americana. A concise and novel synthesis of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one (6) from furfural is described. Photochemical addition of isopropyl alcohol to furan-2(5H)-one afforded 4-(1'-hydroxy-1'-methylethyl)tetrahydro-furan-2-one (3). The alcohol 3 was directly converted into 4-(1'-bromo-1'-methylethyl)-tetrahydrofuran-2-one (5) in 50% yield by reaction with PBr(3) and SiO(2). The final step was performed by cyclization of 5 with potassium tert-butoxide in 40% yield. The novel pyrethroids 8–12 were prepared from methyl (1S,3S)-3-formyl-2,2-dimethylcyclopropane-1-carboxylate (7a) by reaction with five different aromatic phosphorous ylides. Compounds 6–12 presented high insecticidal activity, with 6 and 11 being the most active. Compound 6 killed 90% of S. zeamais and 100% of all the other insects evaluated. Compound 11 killed 100% of all insects tested.

Spectroscopic studies on the photochemical decarboxylation mechanisms of synthetic pyrethroids.

A novel radical trapping technique combined with a fluorescence spectroscopic analysis has been employed to investigate the radical intermediates produced by photodecarboxylation of four synthetic pyrethroids: fenvalerate (SMD), fenpropathrin (DTL), cyphenothrin (GKL), and cypermethrin (AGT). Under photoirradiation at >290 nm, all pyrethroids underwent direct photolysis via homolytic cleavage of the carbon-oxygen bonds in the ester groups. The consumed amount of a nitroxide free radical, as a trapping agent for the intermediate radical of a pyrethroid, was determined by ESR, which was the measure of the reaction yield of a photochemically generated α-cyano-3-phenoxybenzyl radical common to all pyrethroids. The reactivities of the pyrethroids studied was in the sequence of SMD >> DTL > GKL > AGT. Furthermore, nanosecond transient absorption spectroscopy demonstrated that geminate recombination of the radical pair within a solvent cage is the main deactivation route of the photochemically generated α-cyano-3-phenoxybenzyl radical common for all pyrethroids studied.

Synthesis and biological evaluation of pyrethroid insecticide-derivatives as a chemical inducer for Bdnf mRNA expression in neurons.

Brain-derived neurotrophic factor (BDNF) plays a fundamental role in neuronal synaptic plasticity. A decrease of plasticity in the brain may be related to the pathogenesis of neurodegenerative or psychiatric disorders. Pyrethroid insecticides, which affect sodium channels in neurons, are widely used to control insect pests in agriculture and in the home. We previously found that deltamethrin (DM), a type II pyrethroid, increased Bdnf mRNA expression in cultured rat cortical neurons. However, the cyano group at the α-position of type II pyrethroids is likely susceptible to hydrolytic degradation and, its degraded product, hydrogen cyanide, could generate a cellular toxicity in the human body. To determine if the cyano group is required for the Bdnf exon IV-IX (Bdnf eIV-IX) mRNA expression induced by type II pyrethroids, for this study we synthesized a series of derivatives, in which the cyano group at the α-position was replaced with an ethynyl group. Then we added various substituents at the terminal position of the ethynyl group, and biologically evaluated the effects of these derivatives on Bdnf eIV-IX mRNA expression. These ethynyl derivatives induced the Bdnf eIV-IX mRNA expression in a concentration-dependent manner, at varying levels but lower levels than that evoked by DM. The mechanisms for the Bdnf induction and the morphological changes of neurons were the same whether the cyano or ethynyl group was included in the compounds.

Recent advances of pyrethroids for household use.

Development of pyrethroids for household use and recent advances in the syntheses of (1R)-trans-chrysanthemic acid, the acid moiety of most of the household pyrethroids, are reviewed. As another important acid moiety, we discovered norchrysanthemic acid to have a significant vapor action at room temperature when esterified with fluorobenzyl alcohols. In particular, 2,3,5,6-tetrafluoro-4-methoxymethylbenzyl (1R)-trans-norchrysanthemate (metofluthrin) exhibits the highest potency in mosquito coil formulations as well as the vapor action at room temperature against various mosquitoes. Structure-activity relationships of norchrysanthemic acid esters and synthetic studies of norchrysanthemic acid are discussed.

Biotransformation and enzymatic reactions of synthetic pyrethroids in mammals.

Synthetic pyrethroids, a major insecticide group, are used worldwide for controlling indoor and agricultural pests. Extensive mammalian metabolism studies have been carried out since the late 1960s, and major metabolic reactions have been found to be oxidation of the acid or alcohol moiety, ester cleavage, and conjugation reactions. In addition, various conjugation reactions occur in mammals, forming hydrophilic and lipophilic conjugates. Pyrethroids are generally rapidly metabolized in mammals and completely excreted from the body in a short period. Human and laboratory animals share similar metabolic reactions for pyrethroids. Oxidation reactions in humans are mediated by several CYP isoforms. On the other hand, ester bonds of pyrethroids are hydrolyzed mainly by carboxylesterase(s).

Design, synthesis, and insecticidal activities of novel monohalovinylated pyrethroids.

A series of novel monohalovinylated pyrethroids are designed and synthesized to replace one halo atom with a hydrogen atom on the double bond of dihalopyrethroids. Bioassays indicate that some of the synthesized compounds, such as 3j and 1j, exhibit high insecticidal activities against mosquitoes ( Culex pipiens pallens ), oriental armyworms ( Mythimna separata ), alfalfa aphids ( Aphis medicagini ), and carmine spider mites ( Tetranychus cinnabarinus ). Photolytic results of E-cis-1j suggest that monohalovinylated pyrethroids are photodegraded more easily than compound 12.

Sphingobium wenxiniae sp. nov., a synthetic pyrethroid (SP)-degrading bacterium isolated from activated sludge in an SP-manufacturing wastewater treatment facility.

A synthetic pyrethroid (SP)-degrading bacterial strain, designated JZ-1(T), was isolated from activated sludge of a SP-manufacturing wastewater treatment facility and studied using a polyphasic taxonomic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain JZ-1(T) belonged to the genus Sphingobium, showing highest sequence similarities to Sphingobium faniae DSM 21829(T) (98.6 %), Sphingobium cloacae JCM 10874(T) (98.5 %), Sphingobium vermicomposti DSM 21299(T) (97.4 %) and Sphingobium ummariense CCM 7431(T) (96.9 %). The polar lipid pattern, the presence of spermidine and ubiquinone Q-10, the predominance of the cellular fatty acids C(18 : 1)ω7c, C(19 : 0) cyclo ω8c, 11 methyl C(18 : 1)ω7c, C(16 : 0) and C(14 : 0) 2-OH, and the G+C content of the genomic DNA also supported the affiliation of the strain with the genus Sphingobium. Strain JZ-1(T) showed low DNA-DNA relatedness values with S. faniae DSM 21829(T) (30.2 %), S. cloacae JCM 10874(T) (23.3 %), S. vermicomposti DSM 21299(T) (10.9 %) and S. ummariense CCM 7431(T) (7.9 %). Based on its phylogenetic position and its phenotypic and genotypic properties, strain JZ-1(T) represents a novel species of the genus Sphingobium, for which the name Sphingobium wenxiniae sp. nov. is proposed. The type strain is JZ-1(T) ( = CGMCC 1.7748(T)  = DSM 21828(T)).